The underlying disease of gout is hyperuricemia and, after remission from gout attacks, therapeutic modalities to improve hyperuricemia are performed. The therapeutic agents for hyperuricemia are broadly divided into a uricosuric drug and a uric acid synthesis inhibitor (xanthine oxidase inhibitor) and are selected appropriately depending on the status and degree of the disease.
The xanthine oxidase (XOD) inhibitors include 2-phenylthiazole derivatives (patent literature 1 to 6, non-patent literature 1), 3-phenylisothiazole derivatives (patent literature 7, 8), phenylpyrazole derivatives (patent literature 9 to 11), 2-phenyloxazole derivatives (patent literature 12), and phenylheteroaryl derivatives (patent literature 13). The methods of production disclosed in the patent literature 1 to 12 are those wherein heterocyclic rings are formed by linear consecutive reactions and thus, involve a large number of steps. The method of production disclosed in the patent literature 13 is a process wherein the skeleton is formed by direct coupling between a phenyl ring and a heterocyclic ring and, thus involves a small number of steps. However, this method needs to prepare boron compounds and thus results in a higher cost. Therefore, this method is not satisfactory in terms of a low-cost production method with a short process.
As a method of production by binding a heterocyclic ring directly to a phenyl ring at the position of C—H bond on the heterocyclic ring without using boron compounds, there have been reported methods of coupling reactions by using, as a catalyst, palladium compounds (non-patent literature 2 to 8), rhodium compounds (non-patent literature 9), iridium compounds (non-patent literature 10), copper compounds (non-patent literature 11), nickel compounds (non-patent literature 12 to 13), and cobalt compounds (non-patent literature 14). Among them, the method of production by using a nickel compound relates to a method for producing a phenyl-substituted heterocyclic derivative that is a xanthine oxidase (XOD) inhibitor (non-patent literature 12). However, no example has been reported wherein the phenyl-substituted heterocyclic derivative which is the target compound in the present invention was produced by using a metal catalyst other than nickel compounds. Moreover, none of the methods are satisfactory in terms of the restriction of substrate, cost, and yield.
The method of production which directly binds a heterocyclic ring to a phenyl ring at the position of C—H bond on the phenyl ring by using palladium compounds and copper compounds (non-patent literature 15 to 22), or a palladium compound and silver compounds (non-patent literature 23), is well known, but there are many examples wherein copper compounds and silver compounds that are not environmentally preferable are used in an amount equivalent or more to that of the substrate (non-patent literature 15 to 17, 23). In addition, even under the condition of not using the equivalent or more amount of the substrate (non-patent literature 18 to 22), the method is not satisfactory in terms of the restriction of substrate, cost, and yield.
Moreover, no example has been reported wherein the reaction rate is improved by using a palladium compound and a copper compound, or a palladium compound and a silver compound combined with a carboxylic acid.